Introduction

Vaccinations have revolutionised global health by offering protection against many serious diseases upon generations. In countries with high vaccination programme coverage, many of the diseases, especially those that were previously responsible for many childhood deaths have disappeared.^[1] Vaccines exploit the ability of the highly evolved human immune system to recognise, fight and remember encounters with pathogen antigens, so some of them can provide lifelong immunity and others provide immunity that lasts for many years or months, thus they require boosters for continued protection against the disease, those durations of protection depend on the mutation tendency of pathogens.

What is reverse vaccinology?

Traditional Vaccinology

The traditional approach to vaccine development uses two methods: the first one which is used to produce live attenuated vaccines is based on attenuation (weakening) of pathogens to reduce their virulence (the relative ability of a pathogen to cause disease) and the second one which is used to produce non-living and subunit vaccines is based on inactivated or killed antigen, subunit (purified antigen like proteins) and toxoid (inactivated toxins).

Reverse Vaccinology

Is the science that identifies vaccine antigens from the genome of pathogens using the expressed genomic sequences to find new potential vaccines, so the term reverse indicates that vaccine design starts from sequence information without the need to grow pathogens. The genome sequence which is analysed using bioinformatics provides a catalogue of all protein antigens’ genes that the pathogen can express, those genes are filtered to select the best candidate antigens that would make good vaccine targets such as outer membrane proteins. Once the candidates are identified, they are produced synthetically and then screened in animal models of the infection.

Advantages of Reverse Vaccines

• Fast access to every single antigen
• Accelerates the discovery of potential vaccine candidates (PVCs)  
• Non-cultivable microorganisms can be approached
• Nonabundant antigens can be identified
• Antigens that are not immunogenic during infection can be identified
• Antigens that are transiently expressed during infection can be identified
• Antigens not expressed in vitro can be identified
• Non-structural proteins can be used

Reverse Vaccinology Tools

Several tools which are typically follow either filtering or machine learning algorithms have been developed for antigen prediction and vaccine candidate identification such as:

• NERVE: software environment for the in-silico identification of the best vaccine candidates from whole proteomes of bacterial pathogens.
• Jenner-Predict: predict PVCs from proteome or protein(s) sequences for subunit vaccine development.
• Vaxign: vaccine design system that predicts vaccine targets
• VaxiJen: web server predicted the antigenicity of the vaccine design attached with an adjuvant
• VacSol: It is decision-tree software that filters input protein candidates

Reverse Vaccinology Application

The use of reverse vaccinology has enabled identification of numerous promising vaccine candidates such as: vaccines against meningococcus, GBS, group A streptococcus, pneumococcus, pathogenic E. coli, and for antibiotic-resistant bacteria such as Staphylococcus aureus. It also led to the discovery of pili in gram-positive pathogens such as A streptococcus. (Previously, all gram-positive bacteria were thought to not have any pili)

It is believed that within the development of bioinformatics and reverse vaccinology many vaccines that were impossible to develop will become reality.